Contribution of the myosin binding protein C motif to functional effects in permeabilized rat trabeculae.
Myosin binding protein C (MyBP-C) is a thick-filament protein that limits cross-bridge cycling rates and reduces myocyte power output. To investigate mechanisms by which MyBP-C affects contraction, we assessed effects of recombinant N-terminal domains of cardiac MyBP-C (cMyBP-C) on contractile properties of permeabilized rat cardiac trabeculae. Here, we show that N-terminal fragments of cMyBP-C that contained the first three immunoglobulin domains of cMyBP-C (i.e., C0, C1, and C2) plus the unique linker sequence termed the MyBP-C "motif" or "m-domain" increased Ca(2+) sensitivity of tension and increased rates of tension redevelopment (i.e., k(tr)) at submaximal levels of Ca(2+). At concentrations > or =20 microM, recombinant proteins also activated force in the absence of Ca(2+) and inhibited maximum Ca(2+)-activated force. Recombinant proteins that lacked the combination of C1 and the motif did not affect contractile properties. These results suggest that the C1 domain plus the motif constitute a functional unit of MyBP-C that can activate the thin filament.
Razumova
Maria V
MV
Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.
Bezold
Kristina L
KL
Tu
An-Yue
AY
Regnier
Michael
M
Harris
Samantha P
SP
D008841:Actin Cytoskeleton / Q000235:genetics / Q000378:metabolism; D020816:Amino Acid Motifs / Q000235:genetics; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020134:Catalytic Domain / Q000502:physiology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000502:physiology; D009210:Myofibrils / Q000235:genetics / Q000378:metabolism; D015879:Myosin Subfragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs / Q000502:physiology*; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000099163:Myosin Binding Protein C
D002118:Calcium; D002352:Carrier Proteins; D015879:Myosin Subfragments; D011994:Recombinant Proteins; D000099163:Myosin Binding Protein C